The Questioner, who sits so sly, Shall never know how to Reply.
Blake was extremely frustrated with people who tried to pick holes in spiritual things—like his own visions of the spiritual world, for instance—but had no answers themselves. In other poems, he talks about the "idiot questioner," who casually asks skeptical questions without any interest in or desire for a real answer.
He's doing the same thing here. This mini-battle-rap is attacking people who only know how to ask questions (even smart questions) but who have no idea what's actually going on, or how life should be lived, or whether there's a spiritual world, etc.
This couplet doesn't use any metaphors or anything, by the way—it's just a philosophical opinion (or, diss).
He who replies to words of Doubt Doth put the Light of Knowledge out.
This one picks up where the last couplet left off. If you do reply to the "idiot questioner's" idiot questions, you're not doing anything constructive. The questioner has no interest in spiritual realities or the soul or God or any of that stuff—he or she is just interested in asking questions and casting doubt. That's the questioner's jam—and Blake's not blaming him/her for it. He just thinks that's a totally useless way to spend your time.
By trying to answer these questions and doubts, Blake thinks that you're putting "the light of knowledge out" because you're not contributing to the development of real knowledge in any way. You're not convincing anybody, and you're just pouring your time down the drain. It would be worth your time to do something better: to talk to people with an open mind or to, say, write epic poems about the existence of the spiritual realm (like Blake).